Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue

Kanjiro Miyata, Makoto Oba, Mitsunobu Kano, Shigeto Fukushima, Yelena Vachutinsky, Muri Han, Hiroyuki Koyama, Kohei Miyazono, Nobuhiro Nishiyama, Kazunori Kataoka

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Purpose. For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). Materials and Methods. The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. Results. The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. Conclusion. The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.

Original languageEnglish
Pages (from-to)2924-2936
Number of pages13
JournalPharmaceutical Research
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

Fingerprint

Micelles
Block copolymers
Tumors
Genes
Tissue
DNA
Neoplasms
ethylenediamine
Polyethylene glycols
Transfection
Fluorescence
Gene Transfer Techniques
Growth Factor Receptors
Ethylene Glycol
Endothelial cells
Transforming Growth Factors
Dynamic light scattering
Fibroblasts
Luciferases
Biocompatibility

Keywords

  • Gene delivery
  • PEG
  • Polyplex micelle
  • TGF-β inhibitor
  • Triblock copolymer

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

Cite this

Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue. / Miyata, Kanjiro; Oba, Makoto; Kano, Mitsunobu; Fukushima, Shigeto; Vachutinsky, Yelena; Han, Muri; Koyama, Hiroyuki; Miyazono, Kohei; Nishiyama, Nobuhiro; Kataoka, Kazunori.

In: Pharmaceutical Research, Vol. 25, No. 12, 12.2008, p. 2924-2936.

Research output: Contribution to journalArticle

Miyata, Kanjiro ; Oba, Makoto ; Kano, Mitsunobu ; Fukushima, Shigeto ; Vachutinsky, Yelena ; Han, Muri ; Koyama, Hiroyuki ; Miyazono, Kohei ; Nishiyama, Nobuhiro ; Kataoka, Kazunori. / Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue. In: Pharmaceutical Research. 2008 ; Vol. 25, No. 12. pp. 2924-2936.
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AU - Miyata, Kanjiro

AU - Oba, Makoto

AU - Kano, Mitsunobu

AU - Fukushima, Shigeto

AU - Vachutinsky, Yelena

AU - Han, Muri

AU - Koyama, Hiroyuki

AU - Miyazono, Kohei

AU - Nishiyama, Nobuhiro

AU - Kataoka, Kazunori

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AB - Purpose. For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). Materials and Methods. The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. Results. The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. Conclusion. The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.

KW - Gene delivery

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KW - TGF-β inhibitor

KW - Triblock copolymer

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